The chemopreventive action of carotenoids on proteinuria and lymphadenopathy were examined in autoimmune-prone MRL-lpr/lpr(MRL/l) mice. They were fed a synthetic full-fed diet (16–18 kcal/mouse/day) with supplementation ofβ-carotene or astaxanthin (0.19μmoles/mouse, 3 times a week), and the development of lymphadenopathy and proteinuria were examined. MRL/l mice fed a full-fed diet without the supplementation of carotenoids or those fed a calorie-restricted (CR) diet (10–11 kcal/mouse/day, 60% calorie intake of full-fed mice) were employed as controls.CR dramatically delayed the development of proteinuria and lymphadenopathy, as reported previously. Carotenoids also significantly delayed the onset of these symptoms in MRL/l mice fed a full-fed diet. Carotenoids were half as effective as CR and astaxanthin, a carotenoid without provitamin A activity, which appeared to exert more significant preventive actions thanβ-carotene in delaying the development of these symptoms. Similar chemopreventive actions of carotenoids were also demonstrated in MRL/l mice fed a regular diet (Lab Chow). CR has been shown to augment IL-2 production and to decrease serum prolactin levels in this strain, which may be related to its dramatic preventive action of autoimmunity. However, carotenoids did not affect IL-2 production nor prolactin levels in full-fed MRL/l mice.The chemopreventive actions of carotenoids observed in autoimmune-prone MRL/1 mice may be attributed to yet unknown mechanisms, apart from their provitamin A activity or oxygen-quenching activity.