The use of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) to treat transitional cell carcinoma is associated with high rates of granulocytopenia. To test whether the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) would decrease the hematological toxicity of M-VAC 21 patients were treated with standard dose M-VAC (30 mg./m.2 methotrexate on days 1, 15 and 22, 3 mg./m.2 vinblastine on days 2, 15 and 22, 30 mg./m.2 doxorubicin on day 2 and 70 mg./m.2 cisplatin on day 2) plus 5 micrograms./kg. rhGM-CSF subcutaneously on days 4 to 13. On cycles 1 and 2 of therapy grade III or greater granulocytopenia (less than 1.0 x 10(9)/l.) was noted in 39% and 43% of the patients, respectively, and the majority were able to receive the day 15 and day 22 treatments as scheduled. This was an apparent improvement over our historical experience with M-VAC alone (p = 0.03). By cycle 3 of treatment this beneficial effect of rhGM-CSF was no longer apparent, with 80% of the patients experiencing grade III or greater granulocytopenia and thrombocytopenia also becoming apparent. Seven patients had to discontinue rhGM-CSF because of side effects. It is unlikely that clinically significant escalation of chemotherapy dosages can be achieved with M-VAC and rhGM-CSF.