Plant extracts have been widely evaluated for biological properties. In the present study extracts of several native plants in Iran was investigated for their possible immunomodulatory effects. Peripheral blood lymphocytes separated from healthy individuals were stimulated with phytohemagglutinin (PHA) and cultured with different concentrations of the extracts. Comparison of the cell proliferation in treated cultures showed the highest inhibitory effect due to exposure with Linum persicum. This extract caused a strong dose-dependent decrease in lymphocyte proliferation (p < 0.001). Lymphocytes treated with Cirsium bracteosum were inhibited in a dose dependent manner (SI range 0.9-0.2). Similarly, Echinophora cinerea-treated lymphocytes showed a significant reduction in proliferation compared to that in non-treated cells. Among the extracts, Dionysia termeana, Salvia macrociphon and Ferulago angulata had a mild stimulatory effect on the lymphocytes at concentrations less than 1 microg/ml (p < 0.05). At higher doses all these extracts showed significant inhibitory effects on the proliferation of PHA-treated cells (SI range 0.81 to 0.04). In cell cycle analysis performed by flow cytometry, the strongest appearance of apoptotic cells at sub-G1 phase in various extract-treated cultures was found for D. termeana (14.6 +/- 0.5%). The Percentage of cells undergoing apoptosis in cultures treated with L. persicum was more than 11 compared to that of the control (1.7 +/- 0.08). In DNA analysis, D. termeana and L. persicum showed typical DNA laddering, indicating that these extracts induced apoptosis of lymphocytes. In conclusion, all the extracts studied showed lymphocyte inhibitory effects at high concentrations. These inhibitory effects for some of the plants seem to be due to induction of apoptosis.