The effect of oral therapy with 6 quinolones, lomefloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, and CI-990 in the prevention of post-irradiation bacteraemia and mortality was tested in mice. Two models were used, the C3H/HeN mouse strain for endogenously acquired infection and the B6D2FI mouse strain for studies of exogenously acquired Pseudomonas aeruginosa infection. Each therapy or waterfed control group included 40 mice, 20 for monitoring survival and 20 for obtaining liver cultures. In C3H/HeN mice, mortality in the groups that received each of the quinolones except CI-960 was significantly lower (P < 0{dot operator}05) than in the water-treated mice. Survival was 54/60 (90%) with lomefloxacin 51/60 (85%) with ofloxacin, 50/60 (83%) with CI-990, 45/60 (75%) with sparfloxacin, 37/60 (62%) with temafloxacin, 9/60 (15%) for the control group, and 67sol;60 (10%) for CI-960. Enterobacteriaceae were isolated from 38 of 53 (72%) and Streptococcus spp. from 13 of 53 (25%) of the livers of control mice. The number of Enterobacteriaceae was lower in quinolone-treated mice. However, isolation of streptococci was similar to controls, except in those treated with sparfloxacin and CI-990. In B6D2F1 mice, mortality and isolation of P. aeruginosa in each of the quinolone group was significantly lower than for controls (P ≤ 0{dot operator}001). These data illustrate the efficacy of the quinolones in the therapy of exogenous infection, and the inability of those effective against anaerobic bacteria to prevent endogenous infection. © 1994 The British Society for Antimicrobial Chemotherapy.