The effect of topical use of desoximetasone (Topisolon ointment) and triamcinolone acetonide (Volon A cream) for 3 to 4 days on circadian plasma cortisol levels was studied in 22 hospitalized patients (mean age 61 years) for Topisolon, and in ten patients (mean age 59 years) for Volon A. The differences in cortisol levels (RIA) were examined by the frequency distribution analysis of Daeves and Beckel (1958). The need to analyze the features of the distribution curves was clearly demonstrated in preference to simple averaging statistics which rely upon the arithmetic mean as the main parameter. The results suggest two distinct groups of morning plasma cortisol levels - one at a low level of 5.6 X 1.85 +/- 1 and one at a high level of 15.4 X 1.56 +/- 1 microgram/100 ml. The evening level was uniform 6.5 X 2.13 +/- 1 microgram/100 ml. Topisolon depressed the plasma cortisol levels in all groups. Volon A seemed to reduce only the morning high level group to lower values. In addition, Topisolon altered the proportions of patients with high and low plasma cortisol levels, while Volon A had little effect. The different responses of the plasma cortisol levels may imply different kinetics of cutaneous penetration and cutaneous metabolism of the two synthetic corticosteroids.