Retinoids, natural or synthetic derivatives of vitamin A, have been studied as cancer chemopreventive agents and as therapeutic agents in the treatment of solid tumors. Intensive clinical research has focused on the role of retinoids in preventing second primary tumors following head and neck or lung cancer. The frequent occurrence of second primary tumors in these areas provides clinical support for the hypothesis of field carcinogenesis. Based on evidence of its efficacy in reversing oral premalignancy, the synthetic retinoid 13-cis-retinoic acid (13cRA) was studied in a 1-year trial to prevent the incidence of new cancers in patients who had been treated for squamous cell carcinoma (SCC) of the head and neck. Second primary tumors developed in only 4% of 49 patients treated with 13cRA, as compared with 24% of 51 patients treated with placebo (P = .005). These findings have led to two ongoing large-scale trials of 13cRA in North America. One study, performed through the M.D. Anderson Cancer Center and its affiliated Community Clinical Oncology Program and the institutions of the Radiation Therapy Oncology Group (RTOG), will determine whether long-term administration of low-dose 13cRA will prevent second primary tumors following an initial head and neck cancer. Another intergroup study using a similar randomized double-blind design is being performed among patients who have undergone resection of a stage I non-small-cell lung cancer. In Europe, a large chemoprevention study called Euroscan is currently examining the efficacy of another retinoid, retinyl palmitate, in preventing second primary tumors following head and neck or lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)