The distribution of alpha-1-antitrypsin (PI) and vitamin D-binding globulin (GC) phenotypes and gene frequencies has been examined in a homogenous group of clinically well-defined patients (N = 81) with rheumatoid arthritis. The distribution pattern of the two markers was then compared with two control groups consisting of 40 individuals with osteoarthritis and 192 randomly selected normal individuals, drawn from the same geographical area as the rheumatoid arthritis patients. No association was observed between alpha-1-antitrypsin subtypes or deficient alleles and any of clinical variables observed in rheumatoid arthritis cases. Although a slightly high frequency of the GC*2 allele and a low frequency of the GC*1S allele were observed in rheumatoid arthritis and osteoarthritis compared to controls, the differences were not statistically significant. However, within the patients two clinical variables were found to be significantly associated with a particular GC phenotype. Periarticular bony erosions and antinuclear antibody were positively and negatively associated with GC 1S-2 phenotype, respectively.