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In our first experiment we mixed crude supernatant fractions of rat liver that could be activated with azide with fractions of rat brain and rat health, tissues without azide effects on guanylyl cyclase. Mixing extracts of liver with cerebral cortex resulted in an increased azide effect, while mixing liver extracts with heart extracts resulted in a loss of the azide effect. Our interpretation of these data was that azide activation required the presence of other factors present in liver extracts that when added to cerebral cortex permitted azide to activate the enzyme from both tissue extracts. Furthermore, heart extracts possessed a factor(s) that blocked azide activation in the heart extract and in liver extracts in the mixing experiments.