In 1917, spirochaetal neurosyphilis was treated successfully with malariotherapy in combination with salvarsan or bismuth. Malariotherapy for spirochaetal Lyme disease has been discussed, but the mechanism of an antispirochaetal effect remains unclear. We cultured Borrelia burgdorferi at different temperatures, alone and in combination with antibiotics. Our data demonstrate that growth of the strains PKo and ATCC 35210 (B31) was impaired at temperatures of 37 degrees C and inhibited at 39 degrees C and 40 degrees C, respectively. Strain ATCC 35211, however, grew well up to 39 degrees C but did not multiply at 40 degrees C. A bactericidal effect was seen at 41 degrees C for the strains B31 and PKo and at 42 degrees C for all strains. The susceptibility of all strains to penicillin and ceftriaxone was increased up to 16-fold by an elevation of temperature from 36 degrees C to 38 degrees C. These in vitro data suggest that elevated body temperature may be beneficial during antimicrobial treatment of Lyme disease. This may be particularly important in tissues where high concentrations of antibiotics are difficult to achieve.