Daily lysozyme (hen egg) injections, beginning on day 6 of Trypanosoma lewisi infections in rats, significantly reduced the number of circulating trypanosomes. The effect was dose dependent. Maximum reduction (50%) occurred 24 hours after one treatment of 80 mg was given intraperitoneally (I.P.). The same dose of lysozyme was more effective when divided equally into two injections per day. Controls consisting of appropriate buffers as well as human serum albumin had no effect on trypanosome populations. Animals receiving lysozyme exhibited a weight loss of 5% 24 hours following the first injection, but not other ill effects of the treatment were observed. In vitro experiments indicated that lysozyme did not cause lysis or immobilization alone or in combination with fibrinogen or rat antitrypanosomal serum. These results suggest that the cellular immune response of the host and lysozyme's cationic properties may be important in mediating the anti-trypanosomal response. Lysozyme may thus be an effective trypanocide against trypanosomes whose membranes resemble T. lewisi, such as T. cruzi, or as an adjunct to chemotherapy.