We investigated the effect of a somatostatin analogue octreotide (SMS) on the stimulatory effect of recombinant human growth hormone (hGH) on insulin-like growth factor I (IGF-I) generation and growth in hypophysectomized rats. Two weeks after hypophysectomy, treatment was given for 11 days with either saline, SMS (100 micrograms/day), hGH (140 micrograms/day), or hGH plus SMS. Compared with saline-injected controls, hGH stimulated body weight gain [1.1 +/- 0.7 vs. 40.9 +/- 0.8 (SE) g, P less than 0.001] and width of epiphysial cartilage (138.0 +/- 4.5 vs. 356 +/- 3.8 microns, P less than 0.001). Combined treatment with hGH and SMS significantly reduced both body weight gain (29.1 +/- 2.5 g, P less than 0.001) and width of epiphysial cartilage (315.3 +/- 5.8 microns, P less than 0.001) compared with the effects of hGH alone. During 11 days of hGH treatment, serum IGF-I increased from 22 +/- 5 to 1,288 +/- 92 micrograms/l (P less than 0.001) but increased only 40% (513 +/- 71 vs. 1,288 +/- 92 micrograms/l, P less than 0.001) when SMS was given in combination with hGH. In gastrocnemius muscle, heart, and lung, but not in liver, kidney, and brain, SMS suppressed organ weight increase when given both with and without hGH substitution. Thymus and gastrointestinal tract weight were significantly reduced in the group receiving SMS alone and tended to be reduced in the hGH-substituted group given SMS as well. Tissue IGF-I was increased in liver, lung, kidney, and heart with hGH treatment (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)