The sensitivity to heat and chemical modification of human retinoblastoma cells obtained from patients with primary retinoblastoma was studied in vitro by the human tumour colony assay established by Hamburger and Salmon in 1977. Retinoblastoma cells showed moderate sensitivity to 1 h of hyperthermia at 42 degrees C; the median T/C% (ratio of the colony number in treated vs. control dishes, x 100) under hyperthermia was 47.0% for 46 tumours studied. When tumours were treated with melphalan, cis-diamminedichloroplatinum (II), adriamycin, etoposide and teniposide at 37 degrees C and 42 degrees C, the median T/C% for each chemical agent was decreased significantly by concomitant hyperthermia. One-hour exposure of 38 tumours to melphalan, cis-diamminedichloroplatinum (II) (30 tumours), adriamycin (27 tumours), teniposide (22 tumours) and etoposide (20 tumours) at 37 degrees C gave median T/C%s of 9.5, 33.5, 16.0, 3.8 and 38.0%, respectively, while exposure at 42 degrees C gave values of 2.4, 8.2, 5.6, 1.0 and 6.6%, respectively. Combination of heat and chemical treatment with melphalan, cis-diamminedichloroplatinum (II) and etoposide appeared to be synergistic with median T/C%s that were significantly lower than the median T/C%s expected from a simple sum of their individual effects. These in vitro results suggest that combining the treatment modalities of hyperthermia and chemotherapy for primary retinoblastoma would be advantageous.