Plasma immunoreactive atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), serum thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) concentrations were measured in 11 patients with thyrotoxicosis and atrial fibrillation (group 1), in 5 patients with thyrotoxicosis and sinus cardiac rhythm (group 2) and in 8 healthy subjects in comparable age. Patients with thyrotoxicosis were studied before and after treatment with methimazole (3 x 20 mg daily) during 10 days. During treatment sinus cardiac rhythm returned in 6 patients with initial fibrillation (group 1a) while 5 patients still presented atrial fibrillation at the end of the study (group 1b). All patients from group 2 maintained a sinus cardiac rhythm throughout the study. Median plasma concentrations of ANP and cGMP before treatment in patients from group 1 were higher: 43.8 pmol/l and 11.0 nmol/l, respectively than in patients from group 2: 20.0 pmol/l (p < 0.005) and 6.5 nmol/l (p < 0.01), respectively. In all groups of patients methimazole treatment resulted in a significant decrease of plasma ANP and cGMP concentrations in parallel to a reduction of serum T3 and T4 levels. After therapy, plasma ANP and cGMP levels in patients from group 1a were not significantly different from those in patients from group 2, while in patients from group 1b remained slightly elevated. Presented results suggest that atrial fibrillation in patients with thyrotoxicosis represents an important factor augmenting plasma ANP and cGMP levels, in addition to the stimulatory effect exerted by thyroid hormones. However, the marked reduction of serum thyroid hormones produced by short-term methimazole treatment in patients with thyrotoxicosis was associated with parallel decrease of plasma ANP and cGMP levels toward normal values. Therefore, the influence of thyroid hormones on plasma ANP and cGMP concentrations seems relatively more important than the effect of atrial fibrillation.