Atrial natriuretic peptide (ANP) is an important regulator of fluid homeostasis and vascular tone. We sought to compare N-terminal ANP immunoreactivity (ANP-IR) in plasma from cats with and without hypertrophic cardiomyopathy (HCM). Secondarily, we evaluated relationships between ANP-IR and echocardiographical variables in cats with HCM and healthy cats. Venous blood samples were obtained from 17 cats with HCM and from 19 healthy cats. Plasma ANP-IR concentration was determined by an enzyme-linked immunoassay. Two cats with HCM had clinical evidence of congestive heart failure; the remainder had subclinical disease. Plasma ANP-IR concentration was higher in cats with HCM (3,808 +/- 1,406 fmol/L, mean +/- SD) than in control cats (3,079 +/- 1,233 fmol/L), but this difference was not statistically significant (P = .11; 95% confidence interval [CI] = -166 to 1,622). There was a significant, but modest correlation between plasma ANP-IR concentration and left ventricular posterior wall thickness (r = 0.42; P = .01). Additionally, plasma ANP-IR concentration was weakly correlated with left atrial size (r = 0.35; P = .03). A linear regression model was developed to further explore these relationships. Atrial size and wall thickness were included in the model; the 2 explanatory variables had an interactive effect on plasma ANP-IR concentration (R2 = 0.27; P = .02). There was no appreciable correlation between plasma ANP-IR concentration and any other echocardiographical variable. In a population that included cats with subclinical disease, those with HCM did not have significantly higher plasma ANP-IR concentration than did healthy cats. An exploratory multivariable regression analysis suggested a linear relationship between ANP-IR concentration and atrial size, wall thickness, and their interaction.