Combination chemotherapy with gemcitabine and carboplatin administered on a 3-week cycle is used commonly in the treatment of cancer. The purpose of our study was to establish a safe dose of combined gemcitabine and carboplatin when administered on a biweekly schedule to patients with advanced solid tumors. Gemcitabine was given intravenously over 30 minutes followed by carboplatin also given intravenously over 30 minutes once every 2 weeks (one cycle). Five dose levels were examined, ranging from gemcitabine at 1250 mg/m2 to 2000 mg/m2 and carboplatin at an area under the curve of 2.5 to 3.0. Twenty-six patients were studied (18 male and 8 female) with a median age of 57 years (range, 41-83 years); ECOG performance status was 0 or 1 in 22 patients (85%); median number of prior chemotherapy regimens was 2 (range, 0-4); median number of cycles administered per patient was 3 (range, 1-9) with a total of 89 cycles. Two dose-limiting toxicities were observed. Delay in treatment was seen in a total of 8 cycles with 6 of the delays due to myelosuppression. Grade 3 or 4 hematologic toxicity rates were as follows: anemia in one cycle (1%), neutropenia in 13 cycles (15%), and thrombocytopenia in one cycle of chemotherapy (1%). There were no hospitalizations for neutropenic fever. Mild fatigue was the most common nonhematologic toxicity. The median time to progression was 40 days (mean, 49 days; range, 4-133 days). Of the 21 evaluable patients, partial response or stable disease was observed in 11 (42%). The maximum tested dose of gemcitabine at 2000 mg/m2 and carboplatin at area under the curve of 3.0 was well tolerated on a biweekly schedule. Our findings indicate that further investigation of this biweekly regimen is warranted in patients with advanced cancer.