We evaluated cross-sensitization between p-phenylenediamine (pPDA) and p-aminophenol (pAP) or m-phenylenediamine (mPDA) by a modified lymphocyte transformation test. Guinea pigs were sensitized with pPDA using the maximization test procedure. Lymph node cells from the animals were then cultured with pPDA, pAP or mPDA in the presence or absence of epidermal cells (EC). Transformed lymphocyte counts were evaluated by means of 3H-thymidine uptake. Non-sensitized guinea pigs were used as controls. Blastogenesis in lymphocytes from sensitized guinea pigs was enhanced when cultured with pPDA, pAP or mPDA in the absence or presence of EC than without the sensitizers, and the extent of response depended on the concentration of pPDA, pAP or mPDA added to the cultures. Blastogenesis in lymphocytes from control animals was not significantly enhanced in response to pPDA, pAP or mPDA in the presence or absence of EC. The extent of the response to pPDA was greater than that to pAP, which in turn was greater than that to mPDA. In contrast, because pPDA, pAP and mPDA are color developing agents, cross-sensitization between pPDA and pAP or mPDA could not be evaluated by the results of an in vivo challenge due to pigmentation in the patch application sites. The results suggested that there is cross-sensitization between pPDA and pAP or mPDA, and that the modified lymphocyte transformation test is a useful predictive means of detecting cross-sensitization among chemicals, especially for color developing agents.