Paired serum specimens from 149 patients with six different infections verified by a significant rise in the specific antibody level were tested for anticardiolipin antibodies using enzyme-linked immunosorbent assay. Significantly raised levels, at least in one immunoglobulin class, were detected in 32% of the cases, and significant changes in the level indicating an ongoing process, in 26%. Taken as a whole, the response involved the immunoglobulins IgG, IgM, and IgA, although in patients with mumps the significantly raised levels were virtually confined to the IgA class. The binding of syphilitic antibodies to solid-phase cardiolipin was readily inhibited by cardiolipin liposomes, whereas this pattern of reactivity was noted in only one of four nonsyphilitic sera. It was concluded that anticardiolipin antibodies occur very frequently in a wide variety of uncomplicated infections.