The incidence of spontaneous neoplasms in outbred, inbred and F1 hybrid strains was compared using the Charles River-CD rat and mouse, the F344 rat, and B6C3HF1 mouse. These strains are commonly used in carcinogenic studies. Each strain has a consistent pattern of tumor occurrence; testicular, pituitary and lymphoreticular neoplasms are common in F344 rats, mammary and pituitary neoplasms are common in Charles River-CD rats, liver neoplasms are uncommon in CD-1 mice, while hepatic tumors are frequent in male B6C3HF1 mice. There is considerable variation in tumor incidence in individual studies regardless of strain and there appeared to be greater variation in incidence between laboratories using the same strain than in the different laboratories using unlike strains. Therefore, the choice between these strains may be fortuitous or recommended by governmental agencies. Regardless of the strain selected, it is vital to develop sufficient historical tumor data on the strain used at the particular test laboratory.