1. The occurence of biotin deficiency and fatty liver and kidney syndrome (FLKS) in chicks was studied using a 2x2x2x2 factorial-design experiment in which the variables were dietary biotin, fat and protein, and starvation. 2. The severity of biotin deficiency, using growth retardation and severity of dermal lesions as criteria, was least when the low-biotin diet also contained low levels of fat and protein. Addition of fat or protein increased the severity of the deficiency. Tissue fatty acid composition was affected by biotin deficiency only in those birds given the low-protein, low-fat diet. The main change was an increase in the ratio, 16:1 fatty acids :18:0 fatty acids. Plasma glucose and free fatty acid levels in non-fasted birds were unaffected by the dietary variables. 3. Mortality from FLKS with the diet containing low biotin, fat and protein levels was 52% at 28d, but was reduced or eliminated when the dietary level of any of these ingredients was increased. 4. Starvation considerably increased the incidnece of FLKS in the period immediately after fasting, and also affected plasma glucose and free fatty acid concentrations. Liver fatty acid composition, indicated an increase in the proportion of 18:0 at the expense of 16:1 and concentrations increased in proportion, at the expense of 18:0. 5. The relationship between biotin deficiency and FLKS, and a possible mechanism for the induction of FLKS by starvation are discussed.