In this study, the in vitro immunomodulatory effect of concentrated juice of Citrus aurantifolia cv. swingle (Lime) was investigated. Clarified fresh lime juice was concentrated by freeze-drying. After dialysis against phosphate buffered saline and sterilization by a Millipore filter, it was used for further experiments. Immunogenic property of the CLJ extract was documented by production of specific polyclonal antibodies in rabbits. The immunomodulatory effect of the extract was tested in mitogen activated cultured mononuclear cells. The culture results indicated that proliferation of phytohemagglutinin (PHA) activated mononuclear cells were significantly inhibited by 250 and 500 μg/ml of CLJ extract, whereas only 500 μg/ml of the extract could inhibit proliferation of staphylococcal protein A (SPA) activated mononuclear cells (P<0.05). The abrogation of this inhibitory effect of the CLJ extract was noted by adding anti-CLJ antibody to the lymphocyte culture. Considering these data, it can be concluded that the CLJ extract possesses immunomodulatory principles, which may mainly be due to the protein components of the extract.