With eucaryotic cells, butyrate is known to induce a series of morphological and biochemical changes that mimic cellular differentiation. With platelets, we have found that butyrate (10 mmol/l) caused an approximately threefold increase in sensitivity to calcium ionophore A 23187 and arachidonate. Maximum aggregation was observed at agonist concentrations of 3 μmol/l and 170 μmol/l, respectively, as compared with required concentrations of 10 μmol/l and 400 μmol/l in the absence of butyrate. No ultrastructural changes were observed in platelets incubated with butyrate, and the aggregation effects were reversible and returned to normal on removal of butyrate. Butyrate caused a 60% to 70% increase in the uptake of 3H-arachidonate. These results suggest that butyrate may increase the uptake of certain hydrophobic agonists and antagonists by platelets.