In the second Northwick Park Heart Study, cross sectional examination of 2951 middle-aged men confirmed a positive association (r = 0.28, P < 0.0001) between non-fasting serum triglyceride concentration (TG) and factor VII coagulant activity (VIIc). In a sub-sample of almost 700 men, TG was also positively associated with factor VII antigen level (VIIag), factor IX activation peptide (IXp), prothrombin fragment 1+2 (F1+2) and fibrinopeptide A (FPA), although those with the latter two were statistically significant only when adjusted for the effects of within-person variation in plasma concentration (P = 0.01 and < 0.0001 respectively). Plasma Vile was related positively to activated factor VII (VIIa) and VIIag (r = 0.53 and 0.74 respectively). These results are further evidence for increased basal haemostatic activity in the common hyperlipidaemic states. Plasma VIIc and VIIag were also both positively associated with dietary fat intake, independently of TG, in another study of healthy middle-aged men. In dietary experiments, a high-fat meal was followed by a transient increase in VIIa with dose-response characteristics, with no associated rise in VIIag. This response to a fatty meal also occurred in patients completely deficient in factor XII or factor XI, but not in factor IX deficiency. However, factor IX replacement therapy restored the post-prandial responsiveness of factor VII to normal. The intermediary steps in the pathway connecting dietary fat with factor VII through factor IX are poorly understood, but appear to involve lipolysis of plasma TG. The effect of dietary fat on factor VII appears to be largely independent of the far composition. In a study of 26 healthy adults given three isoenergetic diets for three week periods, no significant differences in fasting or non-fasting Vile were found after a high saturated fatty acid diet and a high oleic plus linoleic acid diet. However, mean fasting VIIc was significantly increased after fish-oil enrichment of the unsaturated fat diet in comparison with after the saturated fat diet (98% and 91% of standard respectively; P = 0.004).