Seventy-eight human serum samples were screened for their ability to immunoprecipitate the major (L1) and minor (L2) capsid proteins of HPV1. The L1 and L2 proteins expressed from a recombinant vaccinia virus were able to self assemble into capsids in the nuclei of infected cells. Twenty-eight of the sera precipitated the L1 protein. The L1 protein was only precipitated when the protein was native, denatured protein was not precipitated by the human sera. None of the sera precipitated the L2 protein. The assay demonstrated a significant association between the ability of sera to precipitate the L1 protein and a clinical history of foot warts (P = 0.001). The same serum samples were tested by immunoblots using L1 and L2-trpE bacterial fusion proteins. It was found that almost half of the sera reacted with the L2 fusion protein and few reacted with the L1 protein. Immunoblot results did not correlate well with a clinical history of foot warts (P = 0.7), suggesting that immune precipitation of capsid proteins may be superior to immunoblotting for serodiagnosis of HPV infections.