Nitrate derivatives have in vivo and in vitro platelet anti-aggregant properties in addition to their vasodilatory effects. The mode of action is related to increased intracytoplasmic cyclic GMP concentrations. It has been shown that isosorbide dinitrate (ISDN) has this type of platelet anti-aggregant activity but the reported results about the active concentrations and the inhibited pathways of activation are contradictory. This study was designed to determine whether ISDN has in vitro platelet anti-aggregant activity at low doses and to verify if this effect is selective by aggregation induced by ADP. Finally, a possible potentialisation of the inhibitors due to ISDN was looked for with cyclic nucleotide phosphodiesterase inhibitors and with agents simulating the effect of adenylate cyclase. The results showed that: 1) ISDN had platelet anti-aggregant activity in vitro at concentrations of about 10-7 M, 2) that this effect was not limited to the aggregation induced by ADP as the aggregation induced by PAF-acether was also inhibited by low dose ISDN, 3) of the cyclic nucleotide modulators tested, only quercetine (flavonoide) potentialised the effects of ISDN.