Introduction: We describe two men with marked symptoms following orgasm. In each case, the symptoms were consistent with those found in postorgasm illness syndrome (POIS).

Aim: Further elucidation of the cause of the patients' symptoms.

Methods: Both cases were investigated for causes of POIS with biochemical, hormonal, neurological, autonomic, cardiological, and psychological workup.

Results: Extensive investigation did not reveal a major organic cause for these patients' symptoms. Detailed history revealed likely differing etiologies in each case. In one case, the symptom picture suggested cytokine release, and, in fact, the patient subjectively improved by 80% on taking nonsteroidal anti-inflammatory drugs just prior to and for a day or two after orgasm. The other case appeared to have an ethnic/cultural etiology that was associated with the "Dhat" syndrome.

Conclusion: The apparent differing etiologies/clinical associations of these cases highlight the need for careful history, examination, and investigations in patients presenting with POIS. We recommend that each case needs individual consideration and investigation, and treatment needs to be tailored to the likely cause. It seems likely that POIS represents a spectrum of syndromes of differing etiologies. Further research into the neurobiochemical sequelae of orgasm will be useful in understanding the pathological processes in these cases.