Studies were undertaken to determine whether bovine lactoferrin (bLF) and related compounds, shown to prevent carcinogenesis in the colon and other organs in rats, have any toxic effects in long-term feeding studies. In experiment I, male F344/DuCrj rats received a basal diet containing 0.2% bLF for 40 weeks. No adverse findings were noted, furthermore, serum triglyceride level was significantly decreased to 72% of the control level, suggesting preventive effects against the metabolic syndrome. In experiment II, male and female F344/DuCrj rats were fed a basal diet containing 0.02, 0.2, 2.0 and 5.0% bLF, 2.0% bLF hydrolysate (bLF-H) or 0.1% lactoferricin (LFcin), a peptide derived from bLF, for 60 weeks in males and 65 weeks in females. No toxicological effects, including carcinogenicity, were evident in either sex. The results of the studies provide subjective support for safety of clinical studies of bLF for supplement use.