In a clinical study the blood levels of dehydroepiandrosterone sulphate (DHEAS), pregnenolone sulphate (5-PS), testosterone sulphate (TS) and their respective unconjugated steroids were measured in: 20 patients with systemic lupus erythematosus (SLE) who were receiving either no treatment (11 patients) or else treatment with chloroquine (9 patients), in some cases combined with non-steroidal anti-inflammatory drugs (NSAIDs); in 26 patients receiving corticosteroid (Prednisolone) treatment; and in healthy men and women. The patients not on corticosteroid exhibited substantially reduced DHEAS, 5-PS and TS levels (geom. mean: 2300 vs. normal 4300 nmol/l DHEAS; 200 vs. 320 nmol/l 5-PS; and 120 vs. 360 nmol/l TS; p less than 0.001), irrespective of the difference in sex, age or chloroquine treatment. The patients on corticosteroid treatment displayed a similar pattern of levels, but the reduction was much more marked than in the patients not on the steroid (geom. mean: 610 nmol/l DHEAS, 55 nmol/l 5-PS; and 35 nmol/l TS; p less than 0.001). No consistent changes were observed in the unconjugated steroid levels, although they were also reduced by the treatment with prednisolone. The data indicate that a deficiency in sulpho-conjugated steroids is a permanent feature of patients with SLE and that this is accentuated by the administration of corticosteroid derivatives. Further studies are needed to establish the pathophysiological significance of these findings.