Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentrations < 400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, and 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p < 0.0001) and glucose (p < 0.004) concentrations, body weight (p < 0.02), and age (p < 0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p < 0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p < 0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)