We performed a phase I study combining gemcitabine and interferon (IFN)-&agr;2b in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and recommended doses for phase II trials. Five dose levels of gemcitabine (mg/m2)/IFN-&agr;(×106IU) were planned: 500/5, 1000/5, 1000/7, 1000/10 and 1200/10. Gemcitabine was given once weekly and IFN&agr;3 × weekly for 3 consecutive weeks followed by 1 week of rest (28-day cycles). Between February 1997 and June 1999, 21 patients with advanced pancreatic (n=3), ovarian (n=1), renal (n=10) and non-small cell lung cancer (NSCLC;n=7) were enrolled. The MTD was reached at gemcitabine 1000 mg/m2and IFN-&agr;7 × 106IU, with two of three patients having dose-limiting toxicity (thrombocytopenia). The predominant hematologic toxicities (grade 3/4) were neutropenia and thrombocytopenia (13 and five patients, respectively). Three patients had moderate neutropenic fever and one had grade 4 AST/ALT; none required hospitalization. Of the 18 evaluable patients, responses included one partial response (NSCLC) and 10 stable diseases (eight renal cancer). We conclude that the recommended phase II study regimen is gemcitabine 1000 mg/m2and IFN-&agr;5×106IU, every 28 days. The results, particularly those in metastatic renal carcinoma, are encouraging and worthy of further evaluation in phase II trials.