Malaria epidemics in African highlands cause serious morbidity and mortality and are being reported more frequently. Weather is likely to play an important role in initiating epidemics but limited analysis of the association between weather conditions and epidemic transmission parameters has been undertaken. We measured entomological variables before and during an epidemic of malaria (which began in February 1998) in a highland region of south-western Uganda and analysed temporal variation in weather data against malaria incidence (estimated from clinic records), mosquito density and entomological inoculation rates (EIR). Indoor resting density of Anopheles gambiae s.1. was positively correlated with malaria incidence (r = 0.68, P < 0.05) despite extremely low vector densities. EIR totalled only 0.41 infectious bites per person during the entire 8-month study period. Rainfall during and following the El Niiio event in 1997 was much higher than normal, and rainfall anomaly (difference from the mean) was positively correlated with vector density 1 month later (r = 0.55, P < 0.05). Heavier than normal rainfall associated with El Nifio may have initiated the epidemic; the relationship between temperature and transmission parameters remains to be defined. The results from this study indicate that, in this highland population, epidemic malaria may occur at extremely low inoculation rates.