Platelets can bind HIV and, in turn, be altered in with respect to and function during HIV progression. This study examines the secretion of normal platelets after exposure to recombinant HIV-1MN gp120 or gp41 peptides. There was a modest but significant decrease in regulated upon activation, normal T-cell expressed and secreted protein production in the presence of two out of 10 peptides, which was restored by monoclonal antibodies to gp41. Our data provide novel information on possible primary interactions between platelets and HIV env proteins.