Changes in uterine metabolism and intracellular pH occur with uterine activity and these may in turn alter function. We have investigated the effects of changes in intracellular pH and metabolic inhibition on the spontaneous activity of isolated nonpregnant and pregnant human myometrial strips at 37 degrees C. Intracellular alkalinization resulted in a marked increase in the frequency of contractions in both nonpregnant and pregnant preparations. Intracellular acidification reduced force production in pregnant and nonpregnant preparations. The effects of pH were concentration dependent. Metabolic inhibition (2 mmol cyanide l-1) abolished spontaneous contractions in nonpregnant preparations (ten of ten) but pregnant preparations were able to maintain activity, although at a reduced level (eleven of fifteen). Possible mechanisms involved and relevance to uterine dysfunction are discussed.