The potential of a theory based on organizational memes in coevolution with the environment has been postulated, but remains empirically under-developed. This study explores whether understanding organizational memetic variation is empirically possible and, if so, whether it might, with further development, provide managers with early indications of a misalignment between organizational action (operationalized as memetic variation) and strategic intent—the amount of memetic variation needed to stay aligned with the competitive environment. A method for empirically identifying knowledge-based memes in everyday practice is developed. It stems from modern advances in genetics allowing micro-level changes in genes to be linked to macro-environmental dynamics. Using the concept that memetic variation is caused by everyday, uncontrollable uncertainties of interpretation, memetic variation is reduced to seven categorical types. A highly exploratory quasi-experimental design allows a preliminary comparison of a would-be innovative ‘Portfolio Management Committee’ with self-organizing Internet chat-room settings that are representational of open-source innovation. Results are consistent with predictions showing that higher levels of variation are seen in the latter, despite the former’s strategic intent of innovating to stay aligned with a dynamic environment. Further work is needed, however, to test reliability and validity.