The T cell response to beryllium, measured in bronchoalveolar lavage by the lymphocyte transformation test (LTT), is a critical diagnostic test for discriminating between chronic beryllium disease (CBD) and other granulomatous diseases. We examined the sensitivity, reproducibility, and methods of a less invasive, peripheral blood LTT in 17 patients with CBD and in 18 beryllium-exposed control subjects. Ninety-four percent of CBD cases (16/17) had abnormal blood LTT results, and all 18 beryllium-exposed control subjects had normal blood LTT results. Split samples for 10 beryllium disease cases and eight control subjects demonstrated that the blood LTT was reproducible between two separate laboratories. The LTT was equally sensitive with 10% and 20% serum in the culture medium. We conclude that an abnormal blood LTT can be used to diagnose CBD in patients with compatible lung pathology.