The experiments were designed to elucidate the mechanism of thiopentone-induced inhibition of contractile responses in isolated human epigastric arteries. Segments of human epigastric arteries were obtained from patients who underwent elective or emergency caesarean section, placed in standard physiological salt solution (PSS), cut into rings at 3 mm intervals and suspended in organ baths for recording of isometric contractions at 37 degrees C, and pH 7.4. Three protocols were employed to examine the inhibitory effect of thiopentone: (a) concentration-dependent effect on 10(-7) M noradrenaline (NA)- or high-K+ (40 mM)-induced contractions: (b) effect on NA-induced extra-and intracellular Ca(2+)-dependent contractions and (c) effect on the dose-response curve when Ca2+ is restored to Ca(2+)-depleted rings in Ca(2+)-free 40 mM K(+)-depolarizing medium. Thiopentone (1 x 10(-6) -4 x 10(-3) M) caused concentration-dependent relaxation of both NA- and high-K(+)-induced contractions. The magnitudes of both precontractions were not significantly different but the IC50 values for thiopentone relaxation of high-K+ contractions were significantly lower than for NA contractions. Thiopentone (10(-4) M) significantly attenuated the phasic (intracellular Ca2+ dependent) contractile responses to 10(-5) M NA in Ca(2+)-free PSS as well as the tonic (extracellular Ca2+ dependent) contractions upon restoration of Ca2+. In contrast, nifedipine (1 microM) did not modify the phasic response but significantly attenuated the tonic response. Thiopentone (10(-4) M) also almost completely abolished concentration-dependent Ca(2+)-induced contractions in K(+)-depolarized Ca(2+)-depleted rings. The results suggest that in the smooth muscle of human epigastric arteries, thiopentone-induced relaxation is non-specific and is associated with impairment of Ca2+ supply from both extracellular and intracellular pools.