Purpose Few studies have examined the relationship between weather variables and cryptosporidiosis in Australia. This paper examines the potential impact of weather variability on the transmission of cryptosporidiosis and explores the possibility of developing an empirical forecast system. Methods Data on weather variables, notified cryptosporidiosis cases, and population size in Brisbane were supplied by the Australian Bureau of Meteorology, Queensland Department of Health, and Australian Bureau of Statistics for the period of January 1, 1996-December 31, 2004, respectively. Time series Poisson regression and seasonal auto-regression integrated moving average (SARIMA) models were performed to examine the potential impact of weather variability on the transmission of cryptosporidiosis. Results Both the time series Poisson regression and SARIMA models show that seasonal and monthly maximum temperature at a prior moving average of 1 and 3 months were significantly associated with cryptosporidiosis disease. It suggests that there may be 50 more cases a year for an increase of 1àmaximum temperature on average in Brisbane. Model assessments indicated that the SARIMA model had better predictive ability than the Poisson regression model (SARIMA: root mean square error (RMSE): 0.40, Akaike information criterion (AIC): -12.53; Poisson regression: RMSE: 0.54, AIC: -2.84). Furthermore, the analysis of residuals shows that the time series Poisson regression appeared to violate a modeling assumption, in that residual autocorrelation persisted. Conclusions The results of this study suggest that weather variability (particularly maximum temperature) may have played a significant role in the transmission of cryptosporidiosis. A SARIMA model may be a better predictive model than a Poisson regression model in the assessment of the relationship between weather variability and the incidence of cryptosporidiosis.