Studies of the hormonal status of patients with spondylarthropathies are few in number, despite the predominantly male sex ratio characteristic of these diseases. Most suggested an elevation in androgen levels. We determined the following parameters in 57 men with spondylarthropathies: FSH, LH, prolactin, estradiol, total testosterone, free testosterone, delta-4-androstenedione, 17-OH-progesterone, estradiol over total testosterone ratio and estradiol over free testosterone ratio. Results were compared to those in a group of 100 healthy controls. Mean patient age was 41.9 years, and mean disease duration was one year. None of the patients were under corticosteroid therapy. The mean prolactin level was normal (8.4 +/- 4.5 ng/ml), whereas the mean 17-OH-progesterone level was significantly elevated (2.02 +/- 0.8 ng/ml). The estradiol over testosterone ratios were normal. This hormone profile is consistent with partial deficiency in the enzyme 21-hydroxylase, which is encoded by a gene located on chromosome 6 only 600 kb away from the HLA B locus. We suggest that some class I alleles may be associated with an alteration in 21-hydroxylase responsible for an increase in 17-OH-progesterone levels and for macrophage inhibition resulting in delayed elimination of antigens. This hypothesis is consistent with the possibility raised by others that macrophage inhibition may explain the increased prevalence of infections due to intracellular organisms in patients with spondylarthropathies.