We provide an interim report on pandemic H1N1 influenza activity in South Africa, with a focus on the epidemiology and factors associated with deaths. Following the importation of the virus on 14 July 2009, and the epidemic peak during the week starting 3 August, the incidence in South Africa has declined. A total of 12,331 cases and 91 deaths have been laboratory-confirmed as of 12 October 2009. Age distribution and risk groups were similar to those observed elsewhere. The median age of patients who died (33.5 years) was significantly higher than that of the non-fatal cases (15.0 years, p<0.01). The most common underlying conditions among fatal cases were infection with human immunodeficiency virus (17/32 tested) and pregnancy (25/45 women of reproductive age). Active tuberculosis coinfection was present in seven of 72 fatal cases. These findings should be taken into consideration when planning vaccination strategies for 2010.