The tumor promoting effects of snuff was studied in Lewis rats initiated with 4-nitroquinoline-N-oxide (4-NQO) and Sprague Dawley rats repeatedly inoculated with herpes simplex virus type 1 (HSV-1). The test substances were administered in a surgically created canal in the lower lips of the rats. There were 15 rats in each test group and 10 rats in the control group. In the groups treated with 4-NQO and 4-NQO + snuff, 8 and 12 tumors (5 and 9 malignant) were found, respectively. In the group subjected to HSV-1 only, 3 tumors were found (2 malignant), in the group subjected to snuff only, 4 tumors were found (3 malignant) and in the group subjected to the combination of HSV-1 and snuff, 13 tumors were found (7 malignant). In the control group only one malignancy was found. The study did not show any promoting effects of snuff in the oral cavity after initiation with 4-NQO. Neither was there any increase in the number of oral tumors in rats treated with HSV-1 and snuff. However, there was a marked increase in the number of malignant tumors outside the oral cavity in the group treated with HSV-1 and snuff, underlining the importance of interactions between these two agents in the development of malignant lesions.