Gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP) were assayed in the sera of 27 patients affected with Graves' disease prior to conventional (12-18 months) methimazole (30-5 mg/day) treatment, who were subsequently followed up over 36 +/- 1.5 months (m +/- SEM). Twelve patients underwent recurrence of thyrotoxicosis (relapsers) at variable intervals from withdrawal of treatment, whereas the remaining 12 remained euthyroid (nonrelapsers). In the study group as a whole, both GGT and ALP serum levels were significantly (p less than 0.001) increased with respect to 24 sex- and age-matched euthyroid controls (31.8 +/- 3.6 vs. 11.5 +/- 1.2 U/l and 203 +/- 13.8 vs. 110 +/- 7.3 U/l, m +/- SEM). Prevalence of GGT and ALP elevations was 56% (15/27) and 58% (15/26), respectively. Serum GGT activity was age dependent (r = 0.466, p less than 0.05) and inversely related to log2 microsomal antibody initial titer (r = 0.499, p less than 0.05) in the whole series. There was no difference in mean pretreatment thyroxine (T4) or triiodothyronine (T3) between the groups with supranormal enzyme and normal enzyme levels. However, in the group with enhanced enzyme levels, relapsed patients had higher initial T4 (20.3 +/- 0.8 vs. 17.1 +/- 0.7 micrograms/dl, p less than 0.01) and lower both initial T3 (452 +/- 31.1 vs. 551 +/- 57.8 ng/dl, p less than 0.02) than the nonrelapsed patients. Only in this group, initial T3:T4 ratio was a valuable indicator of the outcome of the disease, since it was below 30 in 7/7 (100%) relapsers vs. 2/8 (25%) nonrelapsers, but above 30 only in 6 subjects who remitted.