The adequate management of cancer chemotherapy side effects continues to be a challenging problem. There is considerable variability in the side effects experienced by different patients to the same chemotherapeutic drugs. Clinical observations and previous findings of neuropathways between the vestibular system and vomiting center prompted this case-control study of whether susceptibility to motion sickness is a determinant of the type and magnitude of the side effects resulting from cancer chemotherapy. Eighty-three of 486 (17%) consecutive patients who were receiving chemotherapeutic drugs as their only treatment for histologically confirmed cancer reported previous motion sickness. Seventy-seven of these study patients were matched to cancer patient controls without previous motion sickness by sex, age, type and dose of chemotherapeutic drug received, and antiemetic medication. Study patients reported significantly greater nausea and vomiting (P less than 0.05), significantly more side effects (P less than 0.05), and a pattern of more frequent, severe, and longer-lasting nausea and vomiting than controls. Susceptibility to motion sickness appears to be a determinant of the side effects of cancer chemotherapy that may prove useful as a clinical marker of those patients who may require more intensive side effect management.