The effect of long-term administration of analogs of luteinizing hormone-releasing hormone (LH-RH) and somatostatin on the growth of the growth hormone (GH)-and prolactin (PRL)-secreting rat pituitary GH3 tumor was investigated. Daily administration of tg/day) (Oss, Holland). Somatostatin analog cyclo(Pro-Phe-DTrp-Lys-Thr-Phe) (Veber cyclic hexapeptide) (12) was synthesized in our laboratory or supplied by J. Sandow and R. Geiger (Hoechst, Frankfurt M, FRG). Somatostatin analog D-Phe-Cys-Phe-t-Trp-Lys-Thr-Cys-Thr-NH2 related to the octapeptide of Bauer (13) was synthesized in our laboratory by solid-phase methods described previously (14).Female Wistar/Furth rats (80-100 g, Harlan SpragueDawley, Indianapolis, IN) were inoculated s.c. in the scapular region with OH3 pituitary tumor cells (obtained from the American Type Culture Collection). The animals were housed 5-7 per cage in a temperature-and light-controlled room. Five to seven animals were used per experimental group. In the first experiment, the treatment with peptides was started before tumors appeared, while in subsequent experiments, peptide administration was initiated when 50-100% of the animals showed well-developed tumors. Tumors were measured weekly with microcalipers and tumor volumes were calculated as described (7). Experiment I. Three days after inoculation of 1 X 106 GH3