The DP receptor-dependence of inhibition of platelet aggregation (PA), degranulation, and TXA2synthesis, by PGD2, in human whole blood, has not been established since selective antagonists have only recently been developed. Accordingly, the effects of PGD2(30 nM), were determined using the DP receptor antagonists AH6809 (50µM) and 868C84 (0.5µM), and results were compared with those obtained using the stable and DP receptor-specific agonist 572C85 (30 nM).With collagen at 0.3µg/ml, PGD2markedly inhibited PA (6 vs 91% PA, p>0.03, n = 12) and both AH6809 and 868C84 alone also inhibited PA but less markedly (62 and 63% PA, respectively) and both antagonists largely prevented the antiaggregatory action of PGD2(57 and 52% PA, respectively). PGD2also markedly inhibited TXB2, formation (reflecting inhibition of TXA2synthesis) (19 vs 48 nM TXB2, p>0.03). AH6809 and 868C84 alone had little effect (both 45 nM) but both antagonists significantly reduced the inhibitory effect of PGD2on TXB2formation (35 and 33 nM, respectively, p>0.03 vs PGD2alone). PGD2also inhibitedβ-thromboglobulin release, but only to a similar extent as with AH6809 and 868C84 alone.With collagen at 3.0μg/ml, PGD2again inhibited PA (60 vs 96% PA, p>0.03), AH6809 and 868C84 alone had no effect on PA (98 and 96% respectively) but effectively abolished the antiaggregatory effect of PGD2. PGD2also inhibited TXB2formation (194 vs 339 nM, p>0.03) and this effect of PGD2was effectively abolished both by AH6809 and 868C84 (313 and 308 nM, respectively). Results obtained with 572C85 largely confirmed those obtained with PGD2, and with collagen at 0.3µg/ml, 868C84 effectively abolished inhibition of both PA and TXB2formation by 572C85.Thus, DP receptor-dependent inhibition of both aggregation and TXA2synthesis both by PGD2and the more selective DP receptor agonist 572C85, was established using the DP receptor antagonists AH6809 and 868C84. Results obtained forβ-thromboglobulin release were inconclusive since both AH6809 and 868C84 inhibited release to a similar extent as did PGD2, indicating that a limited effect either on aggregation or TXB2formation does not preclude a greater effect on degranulation.