Clinically, glucocorticoids are important immunosuppressive hormones. Yet, these steroids are also potent inhibitors of growth. We hypothesized that glucocorticoids may partially inhibit growth by increased somatostatin (SRIF) secretion. We tested this hypothesis using passive immunization techniques. Male rats (approximately 50 g) were treated daily (ip) for 33 days with saline (SAL) or dexamethasone (DEX, 40 micrograms/kg) and every fourth day with normal sheep serum (NSS) or SRIF antiserum (SRIF-ab, 0.25 ml). Body wts were recorded daily. Groups (n = 6) were: 1) SAL + NSS, 2) SAL + SRIF-ab, 3) DEX + NSS, and 4) DEX + SRIF-ab. Regression analysis of the growth curves clearly demonstrated differences in body wt gain for the four treatment groups (P less than 0.01). Final body wt of SAL + NSS treated rats was 285 +/- 5 g and 285 +/- 12 g in SAL + SRIF-ab treated rats. DEX + NSS treated rats weighed significantly less (227 +/- 4 g, P less than 0.01) than SAL-treated rats. This glucocorticoid-induced decrease in body wt was partially reversed by the concomitant treatment of rats with SRIF-ab (241 +/- 6 g, P less than 0.05). This observation leads to the conclusion that the inhibitory effect of glucocorticoids on growth may be mediated, in part, by increased SRIF secretion.