Previous studies in our laboratory have shown that arteriosclerotic changes can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp 65). To investigate the possible regression of such vascular lesions, 63 male New Zealand White rabbits were treated either by triple immunization with fortified Freund's complete adjuvant containing 5 mg/ml Mycobacterium tuberculosis, a hsp 65-rich material, by administration of a 0.2% cholesterol-rich diet only or by a combination of both immunization and cholesterol-rich diet. Sixteen weeks after the first immunization, half of the animals of each group were sacrificed, and as expected arteriosclerotic lesions in the intima of the aortic arch were found in 8 of 10 immunized animals. The remaining animals were sacrificed 16 weeks thereafter, having been maintained on a normal, non-cholesterol-enriched diet from week 16 to 32. Only 3 of 10 rabbits immunized showed moderate lesions in their aortae 32 weeks after the first immunization. On the other hand, atherosclerotic lesions induced by cholesterol-rich diet, or by immunization plus cholesterol-rich diet, showed no significant regression between 16 and 32 weeks. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp 65 can regress in the absence of additional risk factors for atherosclerosis, such as a cholesterol rich diet.