Some patients have persistence of profound fatigue, myalgias, arthralgias without arthritis, dysesthesia/paresthesia, and mood and memory disturbances after standard courses of antibiotic treatment for Lyme disease. This constellation of symptoms has been variously referred to as "chronic Lyme disease," "post-Lyme disease syndrome," and "post-treatment chronic Lyme disease." Persistent symptoms have been reported in patients who are seropositive for IgG antibodies against Borrelia burgdorferi as well as in patients who are seronegative. The cause or causes of persistent symptoms in these patients have not been clearly defined and are controversial. Because of the temporal association of these symptoms with infection with B. burgdorferi, some patients have been treated with prolonged courses of antibiotics. Case reports and uncontrolled trials have reported the efficacy of prolonged antibiotic therapy, often with relapse of the symptoms after discontinuation of therapy. To date, only one randomized, placebo-controlled, double-blind trial of antibiotic therapy for these patients has been published. An abstract of a second placebo-controlled trial of antibiotic therapy in a smaller cohort has also been presented. This paper will describe this patient population in detail and will review the clinical, microbiological, and selected biochemical and immunologic parameters and their responses to antibiotic treatment in the setting of a controlled trial.