Host resistance to Trichinella spiralis infection was compared in rats (F344) and mice (C57BL/6J) following various cyclophosphamide (CY) treatment schedules. Doses of CY given to mice were adjusted by body surface area to be comparable to rat doses. Adult parasite elimination was not affected by oral administration of 1.5, 3 or 6 mg CY/kg/d to rats or 1.05, 2.1 or 4.2 mg CY/kg/d to mice for 10 d. In rats, resistance was suppressed by a single oral dose of 80 mg/kg given the day prior to infection, but was not affected at 20 or 40 mg/kg. A single oral dose of 14, 28 or 56 mg CY/kg did not affect parasite expulsion in mice. Rats were also given 4 daily intraperitoneal (ip) injections of 20, 40 or 80 mg CY/kg/d and mice received 14, 28 or 56 mg CY/kg/d. Infected rats did not survive at the two higher dose levels and parasite expulsion was suppressed at 20 mg/kg/d; parasite expulsion was suppressed in mice by 4 ip injections of 56 mg CY/kg/d, but not by lower doses. In rats, doses oc CY which suppressed adult parasite expulsion also severely suppressed the cellular proliferative response to an extract of T. spiralis (TsE). However, significient suppression of TsE-driven blastogenesis occurred at a dose of CY which did not affect parasite expulsion, indicating that the proliferative response in rats was more sensitive to suppression than actual parasite elimination.