The clinical severity of sickle-cell disease (SCD) is dependent on genetic and environmental variables. Environmental factors have been poorly studied. We have investigated possible links between air pollution and acute pain in SCD. We retrospectively studied the numbers of daily admissions with acute sickle-cell pain to King's College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 admissions over 1400 d (1st January 1998–31st October 2001). Time series analysis was performed using the cross-correlation function (CCF). CCF showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO), low levels of carbon monoxide (CO) and high levels of ozone (O3). There was no association with sulphur dioxide (SO2), nitrogen dioxide or PM10 (dust). The significant results were further examined using quartile analysis. This confirmed that high levels of O3 and low levels of CO were associated with increased numbers of hospital admissions. Low NO levels were also associated with increased admissions but did not reach statistical significance on quartile analysis. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. The potential beneficial effect of CO and NO is intriguing and requires further investigation.