Contractions elicited by CaCl2 on isolated rat stomach strip preparations have been reported to be potentiated by interleukin-1 beta (IL-1 beta). We have investigated whether this effect can be reduced by the putative IL-1 beta antagonist, alpha-melanocyte-stimulating hormone (alpha MSH). Additionally, the effects of alpha MSH on the specific binding of IL-1 beta to B- and T-cells have been investigated to further clarify its inhibitory activities. Both alpha MSH and its carboxyl terminal tripeptide concentration dependently reduced the potentiation of CaCl2-induced contractions caused by IL-1 beta but not those caused by leukotriene D4, the parent molecule being approximately 250 times more active. Additionally, both peptides potently and selectively reduced 125I-IL-1 beta binding to the T-cell sub-clone EL4-6.1 but not to the B-cell sub-clone 1H7. The results indicate that IL-1 beta effects on rat stomach may be mediated through a type-I (80 kDa) IL-1 beta receptor.