The levels of subclass-specific immunoglobulin G (IgG) antibodies to five microbial antigens in normal human sera were measured by enzyme-linked immunosorbent assays (ELISA). The aim was to compare the IgG subclass profiles of specific antibodies to diverse antigens originating from virus, intra- and extracellular bacteria. Serum samples from 162 Danish women were analyzed for IgG1, IgG2, IgG3, and IgG4 antibodies against a peptide of the major outer membrane protein (MOMP) of Chlamydia trachomatis, the native outer membrane proteins of Chlamydia pneumoniae, recombinant membrane proteins of Mycoplasma pneumoniae, recombinant parvovirus B19 capsomers (VP1 and VP2) and C-polysaccharide of Streptococcus pneumoniae (pneumococcus). Antibodies specific for viral and bacterial protein antigens belonged mainly to the subclasses IgG1 and IgG3 while the antibody profile specific for pneumococcal C-polysaccharide was dominated by the subclass IgG2. Antibodies to virus, intra- and extracellular bacteria entering the body via the respiratory tract were found primarily to elicit an IgG1 response. In contrast, antibodies specific for MOMP from C. trachomatis, which infects the urogenital tract, were predominantly IgG3. Our results show that the nature of the antigen and/or the site of colonization or infection have impact on which type of IgG subclass a microorganism elicits.