Alterations of cardiac performance by washed rabbit platelets were investigated in isolated working guinea pig hearts. Enhanced cardiac functions emerged about 5 s after intracardiac injection of platelet suspension (6 x 10(8)-10 x 10(8) cells.ml-1). The LVP, +dP/dtmax, -dP/dtmax, and HR were increased by 30%, 73%, 46%, and 13% (P < 0.05 or 0.01), respectively, and recovered about 10 min later. In the range of 1 x 10(8)-70 x 10(8) cells.ml-1, platelet suspension strengthened the cardiac performance in a concentration-dependent manner. The supernatant demonstrated positive inotropic and chronotropic effects as well, quite similar to those of the suspension. Cimetidine (Cim, 1 mumol.L-1) reduced the cardiotonic effect of the platelet. Mast cell of the isolated guinea pig heart was proven to be in activated state upon 10(9) cells.ml-1 platelet challenge by electron microscopy. Histamine content in platelet suspension measured by HPLC was shown to be 2.6 +/- s 0.7 microgram per 10(9) platelets. It is concluded that histamine, released from platelets and cardiac mast cells, was a key factor in the cardiac alterations.