The effect of He-Ne laser irradiation (lambda = 632.8 nm, dose of 56 J/m2) on the ultrastructure of human peripheral lymphocyte nucleoli has been studied by electron microscopy. After 1 h irradiation, approximately-70% of the lymphocytes examined showed a marked nucleolar response. This consisted of the distortion or fragmentation of the fibrillar center, an increase in the amount of RNP-containing fibrils and granules, and the enlargement of vacuoles. Nucleoli with multiple fibrillar centers and with a strand-like organization of RNP particles were observed in several lymphocytes. The nucleoli increased in size. Based on accepted interpretations of function, the observed changes can be linked to an increase in RNA metabolism including the synthesis and processing of rRNA precursors and the transport of pre-ribosomes from the nucleoli. Similar nucleolar reorganization was observed in parallel experiments using lymphocytes that had been stimulated for 1 h with phytohemagglutinin. Given the lack of mitogenic stimulation of the lymphocytes by He-Ne laser irradiation, the ultrastructural changes induced in the nucleoli by irradiation may be taken to indicate the activation of rRNA synthesis in the G(O) period.