The cell cycle regulators p16INK4 and p15INK4B have been mapped to the minimal region of overlap for chromosome 9p21 deletions, observed in a number of malignancies, suggesting that they could be tumor suppressor genes (TSGs). In the case of p16INK4 this has been further substantiated by the finding of small intragenic mutations. In this study we have investigated the p16INK4 and p15INK4B genes in 16 malignant T-cell lines by means of Southern blot, PCR and sequence analysis. p16INK4 allelic deletions occurred in 15 of 16 cell lines; 12 of which were homozygous and 3 hemizygous. In 1 cell line (DND 41) the remaining p16INK4 allele carried a microdeletion of 29 bp of exon 2, supporting the concept that p16INK4 is a target TSG for deletions on 9p21. Most p16INK4 deletions also included the p15INK4B gene. However, 4 of the cell lines deleted for p16INK4 showed no evidence of p15INK4B loss, indicating that p15INK4B is not the target in these cell lines.