In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21-26 years (mean 23), and old subjects, aged 55-70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin, indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.