We describe here the profiles of antigens of Dirofilaria immitis that are immunogenic in dogs. Purebred beagle dogs were inoculated with a standard number of the infective third-stage larvae of the heartworm. Microfilaremia and anti-heartworm antibody levels were monitored by the Knott's test and by ELISA, respectively. Antibody-binding polypeptides were detected by immunoperoxidase staining of protein blots of detergent extracts of adult parasites from SDS-PAGE gels. Densitometric scans of these blots revealed considerable variation in the profiles of dirofilarial antigens detected by the sera obtained at different stages of the infection. Sera obtained during the prepatent phase, i.e., 3 mo post-infection (titer 1:2000), detected antigens of Mr 75, 80, 100, 130, and 200 kilodaltons. In addition to these antigens, sera obtained at the onset of microfilaremia, 6 mo post-infection (titer 1:30,000), detected antigens of Mr 15, 16, 18, 34, and 38 kilodaltons. Protein blots stained with sera from dogs, which subsequently cleared the microfilaremia and in which the infection became occult, showed that most of the antibody reactivities were directed at antigens of Mr 15, 21, and 38 kilodaltons. The variations in the species of molecules detected in sera obtained during the course of an infection seem to reflect fluctuations in the levels of specific antibodies directed at the individual heartworm antigens. We discuss the apparent role that the metamorphic differentiation of the parasite may play in determining the levels of reactivities of these antibodies at specific stages of the infection.