What are the lessons of the 2016 referendum on UK membership of the European Union (EU) regarding the effects of message framing? This article reports findings from an innovative online survey experiment based on a two-wave panel design. The findings show that, despite the expectation that campaign effects are generally small for high-salience issues – such as Brexit – the potential for campaign effects was high for the pro-EU frames. This suggests that within an asymmetrical information environment – in which the arguments for one side of an issue (anti-EU) are ‘priced in’, while arguments for the other side (pro-EU) have been understated – the potential for campaign effects in a single direction are substantial. To the extent that this environment is reflected in other referendum campaigns, the potential effect of pro-EU frames may be substantial.