A laboratory study in order to establish etiology of acute epididymitis (AE) was made in 243 patients. The complex of etiological diagnosis included: microscopic investigation of urethral discharge or urine, bacteriological examination of an initial urine portion and wound discharge in the operated on patients. In addition, urethral discharge/urine was studied with polymerase chain reaction (PCR) in 96 patients; in 46 men PCR examined operative material. It was found that in sexually active young patients AE was caused primarily by infectious agents of sexually transmitted diseases. Targeted etiotropic therapy results in clinical cure in the majority of the cases. In older patients the disease was of bacterial origin (gram-negative bacteria, as a rule, are causative agents) and in some cases is associated with development of pyodestructive epidydimitis.