An in vitro assay system that mimics some of the features of in vivo oral methoxsalen photochemotherapy (PUVA) in relation to human lymphoid cells was developed. In this assay, suspension cultures of human lymphoid cells were subjected to therapeutic concentrations of 8-MOP and to a UVA radiation spectrum modified to approximate the dermal exposure. The assay permitted correlation and quantitation of multiple 8-MOP plus UVA-induced biological and physical alterations in the same assay system. Thus were demonstrated inhibition of DNA synthesis, reduction of cell survival, production of DNA cross-links, and loss of mixed leukocyte reactivity induced by combinations of 8-MOP and UVA in or near the presumed therapeutic range. This assay may be useful for predicting lymphoid cellular toxicity of other photoactive agents as well as for examining the molecular effects of these agents.