In a previous study, we demonstrated that cationic liposome-encapsulated doxycycline (CaL-Dox) was two-fold more effective than free doxycycline against Chlamydia trachomatis in vitro. Here, we evaluated the effects of two CaL-Dox regimens in comparison with unencapsulated doxycycline on the course of chlamydial genital infection in mice. Progesterone-treated, female CF-1 mice were challenged intravaginally with 1.2 x 10(5) inclusion-forming units (ifu) of C. trachomatis. Two days post-infection, the animals were divided into four treatment groups for im injection of doxycycline at 10 mg/kg body weight bd for 3 (3 Dox) or 7 days (7 Dox), or of CaL-Dox at the same dose level for 3 (3 CaL-Dox) or 7 days (7 CaL-Dox) consecutively. An infected fifth group served as a control and was given an empty CaL preparation. C. trachomatis were isolated after five blind passages from 82% of infected control mice, 61.4% of 3 Dox, 52.2% of 3 CaL-Dox, 29% of 7 Dox and 20% of 7 CaL-Dox animals. Histopathological reactions were found in various tissues of the genital tract in 79.5% of infected control mice, 80.9% of 3 Dox, 65.2% of 3 CaL-Dox, 47.1% of 7 Dox and 25.7% of 7 CaL-Dox animals. Total antichlamydial antibody titres were lower in 7 CaL-Dox mice than in all the other groups (P < 0.005). The results showed that progesterone-treated CF-1 mice are suitable for investigation of both lower and upper genital tract infection with a lymphogranuloma venereum biovar strain of C. trachomatis. Neither 7 CaL-Dox nor 3 CaL-Dox treatment was more effective than unencapsulated 7 Dox doses in the bacteriological cure of chlamydial genital infection in mice. However, 7 CaL-Dox prevented tissue damage in the genital tract significantly more than all the other regimens (P < 0.05). These results suggest that liposome-encapsulated doxycycline, particularly CaL-Dox, may have potential for the clinical treatment of chlamydial infections.