RMI 9563DA inhibited the classical complement pathway in rat serum in vitro with an 150 of 51 micrograms/ml in diluted serum and 750 micrograms/ml in undiluted serum. Tilorone was much less active than RMI 9563DA in diluted serum and was inactive in undiluted serum. No complement inhibition could be detected in vivo following a near lethal dose of RMI 9563DA (25 mg/kg i.v.). Thus, complement inhibition is not the mechanism by which these compounds exert their anti-inflammatory activity. Both compounds increase serum hemolytic complement activity 24 h after administration to rats. With RMI 9563DA, this effect is entirely due to the local irritancy produced by s.c. administration of the compound. Tilorone, however, has a specific effect on complement synthesis which may be related to its ability to induce interferon.