Antithyroglobulin (anti-Tg) antibodies cytophilic for human monocytes were detected in the serum of 30 of 45 patients with Hashimoto's thyroiditis using the passive rosette technique. These antibodies conferred on normal monocytes the ability to form rosettes with Tg-coated erythrocyres (E-Tg) in vitro. The percentage of E-Tg rosette-forming monocytes was correlated with serum anti-Tg antibody titers measured by tanned sheep red cell hemagglutination. Most serum cytophilic activities were recovered in the immunoglobulin G fraction and were not affected by heating to 56 C for 30 min or ultracentrifugation at 105,000 X g for 60 min. Passive E-Tg rosette formation by monocytes was immunologically specific and was inhibited by the addition of small amounts of free Tg into the medium but was not inhibited by the addition of normal human serum. The anti-Tg antibody-armed monocytes became cytotoxic against Tg-coated chicken erythrocytes and lysed target erythrocytes by an extracellular mechanism. It was suggested that monocytes might be armed by cytophilic antibodies in vivo, since monocytes of patients with Hashimoto's thyroiditis showed increased E-Tg binding (rosette formation) relative to monocytes from control subjects. These findings support the possible pathogenetic involvement of monocytes in human autoimmune thyroiditis.