['Cell proliferation rates represent a central element in the promotional phase of carcinogenesis. Modified alternate-day fasting (ADF), i.e., a partial 24-h fast alternated with 24-h ad libitum feeding, reduces global cell proliferation rates on a low-fat (LF) diet. Because the majority of Americans consume a diet that is high in fat, testing the antiproliferative ability of ADF on a high-fat (HF) diet is important in terms of diet tolerability in humans. Accordingly, we examined the effects of 85% restriction on the fast day (ADF-85%) with an LF or HF background diet on proliferation rates of various tissues.', 'In a 4-wk study, male C57BL/6J mice were randomized to one of three groups: 1) ADF-85%-LF, 2) ADF-85%-HF, or 3) control.', 'Body weights of the ADF mice were similar to that of controls throughout the study. A hyperphagic response (P < 0.001) was noted only in the ADF-85%-LF group ( approximately 55% more food consumed on the feed day than controls). No differences were noted for mean energy intake between ADF groups on feed or fast days. Equivalent reductions (P < 0.01) in epidermal, prostate, liver, and splenic T-cell proliferation rates were observed in both ADF groups versus controls. Plasma insulin-like growth factor-1 levels decreased (P < 0.05) similarly in both ADF groups. Insulin-like growth factor-1 mRNA levels were not affected by either treatment.'] Does alternate-day fasting reduce global cell proliferation rates independently of dietary fat content in mice?