In a previous report, we have identified interleukin-1 alpha (IL-1 alpha) in amniotic fluid of women with premature rupture of the amniotic membrane (PROM), and suggested that this cytokine may play a role in the development of the fetus. To clarify the functional role of amniotic IL-1 alpha, we studied its effect on the induction of nitric oxide (NO) synthesis in the uterus. IL-1 alpha administered intraperitoneally to rats induced an increase in the amount of mRNA encoding the macro-phage-type iNOS which was determined by reverse transcription-polymerase chain reaction. NO measurement by NO selective electrode revealed that NO production in the rat and human uterus treated with IL-1 alpha was promoted by the addition of 1 mM L-arginine to the culture medium. These findings suggest that in women with PROM, amniotic IL-1 alpha may reduce uterine contractions, in part, by inducing of iNOS.