The aim of this investigation was to characterise the effects of ATP analogues and UTP on the single cell intracellular Ca2+ concentration ([Ca2+]i) in cultured rat mesangial cells. Typically, there were two phases in the Ca2+ response to the agonists, an initial fast transient peak and a subsequent slower decline, or plateau, phase. For the peak amplitude in [Ca2+]i the agonists had about equal effect. But when taking in consideration the percentage of responding cells and the integrated Ca2+ response over 1 min, the order of efficacy of nucleotide agonists (100 microM) was UTP = ATP > ATPgammaS > ADP = 2MeS-ATP (2-methylthio-ATP). Adenosine, AMP and beta,gamma-Me-ATP (100 microM) had no effect. Suramine (100 microM) and reactive blue (50 microM) decreased the number of responding cells. Removing Ca2+ from the bath diminished neither the peak in [Ca2+]i nor the percentage of responding cells, but the average [Ca2+]i increase in 1 min was significantly reduced. The results indicate that P2Y2 receptors are present in rat mesangial cells but it cannot be excluded that there are receptors distinct from P2Y2 which also mediate a rise in [Ca2+]i.