The effect of ortho-vanadate on Ca(2+)-influx in the uterine smooth muscle was investigated. Orthovanadate (10-300 microM) gradually increased the muscular tone of rat isolated uterus bathed in a high K+ (30 mM)-low Ca2+ (0.15 mM) solution. This response was blocked by nifedipine (10 nM) and reproduced by BAY K 8644 (3-300 nM). Atropine and indomethacin were unable to block the effects induced by vanadate and BAY K 8644. Cumulative addition of CaCl2 to the tissue bathed in a depolarized solution without CaCl2 produced a graded tonic response that was potentiated by either vanadate (30 microM) or BAY K 8644 (30 nM), and inhibited by nifedipine. Neither vanadate (30 microM) nor BAY K 8644 (30 nM) modified the uterine tone of tissues immersed in the depolarizing solution without CaCl2. It is concluded that vanadate-induced contraction of rat uterine smooth muscle involves Ca(2+)-influx from the extracellular medium to the myometrial cell. Vanadate might act as a Ca(2+)-channel activator, similar to BAY K8644.