Between May 1985 and July 1987, 49 skin reactions of 43 patients treated by proton irradiation were observed at the Particle Radiation Medical Science Center (PARMS), The University of Tsukuba. Taking the peak skin score as an endpoint, the radiobiological effects [relative biological effectiveness (RBE) and time-dose relationships] of the proton beam in multi-fractionated treatments were estimated. Factors influencing the skin dose, such as the prescribed tumor dose, tumor site, and number of applied fields, were also analyzed. The following conclusions regarding acute skin reactions to the clinical use of proton irradiation were obtained: 1) the physical skin-sparing effect of proton irradiation in single-field irradiation, especially in superficial regions, is not large compared with that of high-energy photon irradiation; 2) multidirectional proton irradiation significantly reduced the skin dose and severity of acute reactions; 3) the radiobiological effects of the proton beam, RBE and the time factor, estimated in human skin in multi-fractional treatment were slightly smaller than those of X-rays, i.e., 0.92 and -0.25 +/- 0.09, respectively.