Adenocarcinoma of unknown primary origin (ACUP) is a common oncologic problem for which there is no standard therapy. Forty-two patients with metastatic tumor were identified as having ACUP after extensive evaluation failed to reveal a primary site of disease. They were treated with an investigational chemotherapy regimen consisting of vindesine and doxorubicin. Of the 38 evaluable patients, six (16%) had major responses to chemotherapy. The median duration of response was 4 months. The median survival of the responding patients has not been reached, but is greater than 8 months. The median survival of the nonresponding patients was 6 months. Vindesine and doxorubicin were well tolerated. The major toxicity was leukopenia, with a median wbc count nadir of 2600/mm. We conclude that the combination of vindesine and doxorubicin has some activity in ACUP, but does not improve the response rate seen with other regimens.