Ionising radiation can induce responses within non-exposed neighbouring (bystander) cells, which potentially have important implications on the estimates of risk at environmentally relevant doses. Using human skin fibroblasts (AG1522), a range of methods were used to investigate the nature of the signal(s) arising from the exposed cells. The signal(s) can be transmitted by direct cell-cell communication (investigated by using partial dish irradiations) or by medium-borne factors (a co-culture system where two monolayers share the same medium but only one monolayer is exposed to ionising radiation). CDKN1A was found to be up-regulated in both directly exposed and non-exposed cells. The data suggest that direct cell-cell communication dominates for these confluent cells, with medium-borne factors also contributing.