There is evidence that cyclic AMP mediates the secretion of adenohypophysial hormones induced by hypothalamic releasing hormones (Labrie, Pelletier, Lemay, Borgeat & Burden, 1973), that mammary gland explants respond to prolactin with increased levels of cyclic AMP (Scott & Howard, 1975), and that prolactin enhances adenyl cyclase activity when incubated with prostate homogenate (Golder, 1972). We therefore decided to examine the possible role of cyclic AMP in a local and highly specific effect: mediating stimulation of the pigeon crop sac by prolactin. Using this model it had already been demonstrated that ATP or GTP, but not cyclic AMP, potentiates the stimulatory effect of prolactin on proliferation of the pigeon crop sac (Sinha & Schmidt, 1970).Fifty adult male and female common pigeons (Columba livia domestica), weighing 500 ±50 g each, were housed in single cages and given access to grain and water ad libitum. Two weeks after capture the pigeons were divided into five groups, ten birds per group. Ovine prolactin N1H PS-9 (30-3 i.u./mg) was dissolved in minimal amounts of 0-1 M-NaOH, as suggested by NIAMDD, brought to a final volume of 0-4 ml/pigeon with 0-9% NaCl solution, and injected into four groups of pigeons in 0-1 ml amounts twice daily for 2 consecutive days.The total doses administered were 0 5, 0-1, 0-2 and 0-4 i.u./pigeon respectively. All solutions were injected intradermally over the right halves of the pigeon crop sac, while the left crophalves were injected with saline. The fifth group (controls) was injected with 0-002 M-NaOH solution, the recommended prolactin solvent. No side-effects (i.e. local inflammations) were recorded on any of the experimental pigeons. The pigeons were killed by decapitation, their crop-halves weighed, cut in small pieces, soaked in ice-cold Krebs-Ringer-bicarbonate buffer solution ( 7·4), 2-5 ml/g, and homogenized for 2 min. After adding trichloroacetic acid (TCA) to a final concentration of 5 %, the homogenates were centrifuged at 1000^for 20 min, 0-1 ml M-HC1 was added the the TCA extracted with diethyl ether. The residual ether was evaporated in a water bath at 55°C. Aliquots of this solution were evaporated to dryness with nitrogen, and cyclic AMP was determined according to the method of Gilman (1970), modified by using charcoal plus 2% bovine serum albumin to separate the bound from the free nucleo¬ tide as suggested by Brown (1971). The binding protein was prepared from rabbit muscle following the procedure of Miyamoto, Kuo & Greengard (1969). The recovery of cyclic AMP added to the tissue was 90 ± 7-2 %. Cyclic AMP values are expressed as pmol/g wet tissue.Ovine prolactin at each of the four doses which caused local proliferation of the crop mucosa markedly increased the cyclic AMP content of the treated crop-halves as compared with the saline-injected halves (Table 1). No difference in cyclic AMP concentration was observed between the two crop-halves of the control pigeons. These findings suggest that cyclic AMP may be a mediator in the proliferative effect...