The activity of cefazolin (CEZ) and cephradine (CED) was studied in experimentally infected neutropenic mice. Neutropenia was induced by 600 rad whole-body irradiation; an infection was induced by the injection of 5 X 10(6) Escherichia coli into the thigh on Day 5 after irradiation. Antibiotics were administered 1 h later, and antibacterial activity was estimated from bacteria counts made in the homogenized individual thighs 3 h after infection. The effect of a low dose of each of the cephalosporins on the infection was significantly lower in the absence of granulocytes than in animals with intact host defence; at higher dosages the effect of both antibiotics on the infection was the same in neutropenic and unirradiated mice. In the neutropenic mice, CEZ was 2.95 times more active than CED against E. coli in vivo, this difference in activity being similar to that found earlier in normal mice.