Three stages can be observed in Lyme borreliosis: the acute stage (with dermal and systemic disease), an intermediate stage (with neurological and cardiovascular complaints and myositis), and a chronic stage (with arthritis, low back pain, dermatological and neurological complaints). If no acute stage with erythema chronicum migrans is seen, laboratory tests must provide the diagnosis. In the so-called two-test protocol at least two different tests must be positive for a definite diagnosis. Because culture is difficult, serology (demonstration of specific IgM and IgG antibodies against spirochaetal antigens) is the preferred technique. Cross reactions, antigenic variations and differences in antigenic expression in American and European strains may cause false-negative and false-positive results with the current tests. Moreover, previous use of antibiotics can interfere with the production of specific antibodies, and the effect of therapy is not correlated with height and behaviour of antibody titres. Additional investigation with immunoblot techniques, demonstrating specific antibody patterns may be valuable. An interesting alternative, not yet fully developed, is detection of specific antigens in tissues.