The case studies of four patients, two men and two women between the ages of 42 and 54 years, are described. They presented to a hospital emergency department during the summer months with acute fever and exanthema. These are the primary symptoms of Mediterranean spotted fever (MSF), an endemic rickettsial disease in the Mediterranean basin that is seen particularly during the summer. The patients were clinically diagnosed as having MSF, but their diagnoses were not confirmed by serological testing. One patient was diagnosed with primary human immunodeficiency virus type 1 infection (HIV-1) 10 days later. The remaining three patients were diagnosed with HIV infection years later, but it is very likely that they also had primary HIV infection when MSF was presumed. When a patient develops sudden onset of fever and a maculopapular rash that is characteristic of MSF, the possibility of primary HIV-1 infection should be considered.