Acetate has a stimulatory effect on the renal cortical p-aminohippurate transport system in vitro (1) and in vivo (2). This effect was first interpreted as a direct effect on metabolism related to the transport system (1-3). In fact, Cross and Taggart (1) suggested that the stimulation of p-aminohippurate accumulation seen in adult kidneys indicates that acetate is one of the ratelimiting cellular components involved in the transport system. On the other hand, Schachter et al. (4) suggested that acetate enhances p-aminohippurate uptake by its conjugation with glycine to form acetylglycine, which functions to relieve a normal degree of competitive inhibition by long chain acylglycines . The suggested relative specificity rendered by acetate (1-4) as a stimulatory agent was challenged by Koishi ( 5 ) who showed that acetate inhibited, as well as stimulated, p-aminohippurate uptake, and that pyruvate, succinate, and aketoglutarate quantitatively mimicked the effects elicited by acetate. The controversy concerning the role of acetate in the active uptake of weak organic acids by the kidney prompted us to perform comparable studies using p-aminohippurate as a model weak organic acid in order to elucidate the specific function of acetate.Material and methods. Adult New Zealand rabbits weighing from 2.5 to 4.0 kg were used in this investigation. After the rabbits were sacrificed by injecting air through an auricular vein, the kidneys were immediately removed and placed in an icecold (0") low-Na (10 mM) Cross-Taggart medium devoid of acetate. Renal cortical slices, approximately 0.3-0.5 mm thick and weighing 200-300 mg, were cut with a Stadie-Riggs tissue slicer and then were randomly divided into two groups. One group was transferred to a modified low-Na Cross-Taggart preincubation medium containing 10 mM acetate, whereas the other was transferred to a similar preincubation medium devoid of acetate. Preincubation was done at 0" for 30 min. The groups of slices were incubated in their appropriate high-Na (100 mM) modified Cross-Taggart medium containing p-aminohippurate, in either the presence or absence of 10 mM acetate, respectively. The compositions of the 10 and 100 mM Na media have previously been described (6). In the nonacetate series, sodium acetate was replaced by an equimolar amount of NaCl. All preincubations and incubations were performed under 100% 0,. The incubations were done in a Dubnoff metabolic shaker at either 25 or 37" for 45 min.Three different types of experiments were performed. In the first series of experiments, the effect of acetate on p-aminohippurate accumulation and oxygen consumption at both 25 and 37" was examined. Groups of slices were preincubated and incubated in either the presence or absence of acetate. In the accumulation experiments, the slices were blotted and weighed at the end of the incubations; the calculations were based upon this wet weight. In the oxygen consumption experiments, the slices were blotted and weighed prior to incubation. Oxygen uptake was represented on the bas...