A single nucleotide T to C transition of the gene encoding glycoprotein IIIa leads to a common diallelic polymorphism Leu-33-->Pro (PLA1/A2). We studied the relationship between the PlA1/A2 polymorphism and platelet function in 80 healthy men, aged 20-25 years. Before aspirin ingestion, bleeding time (BT) was shorter in carriers of the PlA2 than in carriers of the PlA1/A1 allele. At 4 h after ingestion of 300 mg of aspirin, BT became prolonged, and the intergroup difference was enhanced. In seven out of 26 PLA2 allele carriers, aspirin shortened BT on average by 30 s, compared with only one among 54 subjects with the PlA1/A1 genotype. Thus, BT both at baseline and after aspirin depends on the PlA1/A2 polymorphism of glycoprotein IIIa. Carriers of the PlA2 allele appear to be more resistant to the antithrombotic action of aspirin.