1. Spontaneous locomotor activity of four mouse strains, the albino ICR, BALB/C, the black C57 BL/6 and the brown CDF-I, was studied in conjunction with whole brain content of select biogenic amines and major metabolites. The ICR and C57BL/6 mice scored the highest and lowest motility among the strains studied, respectively. 2. The ICR mice motility were the most sensitive to experimental stress among the mouse strains evaluated. 3. Brain dopamine concentrations were greater in ICR and CDF-I mice than the other two mouse strains. This is compared to high serotonin and 5-hydroxyindole acetic acid levels determined in C57BL/6. 4. A relationship between the ICR mouse strain with a high motility and the ratios of brain dopamine:homovanillic acid and between serotonin:5-hydroxyindole acetic acid was established. 5. An inverse relationship between ICR mice motility and the ratio of metanephrine and normetanephrine:3-methoxy-4-hydroxyphenylglycol (MHPG) was determined. 6. It is concluded that genetic predisposition may account for a relationship between motor activity and brain biogenic amines which may give insight into the susceptibility of different patients to the development of certain extrapyramidal diseases.