An in vitro assay, which evaluates the effect of drugs on labelled DNA precursor incorporation into fresh specimens after 3 h of in vitro treatment, was used for a prospective study. Drugs were used as monochemotherapy or in different combinations according to their in vitro activities for salvage or palliation treatment of 16 patients with germ cell testicular tumors, for a total of 21 correlations between in vitro and clinical results. In 11 instances, drugs active in vitro were used; in 10 instances, because no drug was active in vitro, patients were treated with inactive drugs. There was a significant correlation between in vitro and clinical activity (p = 0.02), with a very high true-negative rate (90%) and a lower true-positive rate (54%). No patient treated with drugs inactive in vitro survived 2 years, whereas freedom from progression and overall survival for patients treated with drugs active in vitro were 27.3 and 36.4%, respectively (active vs. inactive, p = 0.007). The overall response in the group of patients treated prospectively was comparable to that observed in a group of 9 patients treated in the same period of time with drugs of unknown in vitro activity (33 vs. 11% objective and long-term responses, respectively, p = n.s.) notwithstanding the high percentage of patients treated with drugs inactive in vitro in the former group.