A new method for the study of drug–cell interaction is suggested. It is based on optical monitoring of cell response to drug impact. To detect this response, a high sensitive photothermal imaging technique has been developed. This technique is based on irradiation of the cells with a focused short pulse double-frequency pump laser (532 nm, 8 ns) and monitoring the laser-induced local thermal effects. This is realized with a second collinear dye laser pulse (630 nm, 6 ns) that probes the heated cell absorbing zones. The temperature-dependent variations of the refractive index in the absorbing zones in cross section of probe beam are recorded with phase-contrast technique. The photothermal (PT) image represents a two-dimensional depth-integrated temperature distribution in the irradiated volume and correlates with the conventional optical absorption images. It was experimentally shown that the introduction of or anti-tumor drug in the cell suspension led to a change in the structure of PT images of human lymphocytes and human lympholeukemia cells, respectively. It was hypothesized that the observed effects could be associated with the change of redox state of respiratory chain component. © 2002 Society of Photo-Optical Instrumentation Engineers.