Studies suggest that there is an association between weather patterns and ischemic stroke risk. Exposure to a sudden decrease in temperature may increase stroke risk through altering blood viscosity and/or by triggering infections. We investigated the association between ischemic stroke risk and change in temperature. We used a case-crossover study design with 303 consecutive patients admitted to Heidelberg University, Department of Neurology over a one and a half year period (Aug 1998-Jan 2000). We used one day before stroke as the hazard (case) period matched to two control periods 2-7 days before and after stroke onset and took both ambient maximum temperature and the 24-hour difference in maximum temperature as exposure. There was no risk associated with ambient maximum temperature at all lag times and in all subgroup analyses. For the 24-hour difference, large changes in temperature (>5 degrees C) were associated with an increased risk of acute ischemic stroke regardless of whether the change was negative or positive. The odds ratio for temperature increases >5 degrees C compared to no change in temperature was 2.0 (95% confidence interval (CI): 0.7-5.9) at a lag time of 3 days. We found no relevant relation between temperature and stroke risk. The results suggest that the risk of ischemic stroke may increase with large day-to-day variations upwards or downwards in temperature.