Exposure to power frequency magnetic fields [EMF] has been proposed as a casual factor in the induction of a wide range of adverse health effects, including cancer. However, although the EMF epidemiology is suggestive, no conclusive data exist to support this hypothesis. To date, most in vivo experimental studies of EMF bioeffects have used an idealized metric in which animals are exposed continuously to pure, linearly polarized 50 or 60 Hz sine waves. A key limitation to the design of these studies, however, is that they use a highly idealized exposure metric that does not include several components of environmental EMF to which humans are routinely exposed. To address this critical data gap, we propose to investigate the biological activity of complex EMF metrics that include power frequency harmonics, transients, and time-varying magnetic fields, using pineal function in rats as a biomarker. Alterations in pineal enzyme activity and decreased serum melatonin have been implicated as potentially causal in carcinogenesis, reproductive dysfunction, and other adverse health effects; pineal function can be quantitated precisely, and is modulated by exposure to physical factors. As such, pineal function provides a sensitive in vivo biomarker with which to study EMF effects. The goal of the program is to identify biologically active EMF metrics other than continuous 60 Hz sine waves, in order to support a more complete assessment of the health effects of EMF exposure. The program will investigate two hypotheses: (1) superimposition of power frequency harmonics or transients onto a pure 60 Hz magnetic field will induce biological responses that are not induced by exposure to pure 60 Hz magnetic fields alone, and (2) rapidly intermittent or time-varying exposure to EMF has biological activity that is not seen with continuous EMF exposure. To investigate these two hypotheses, timed-sacrifice studies will be performed to quantitate pineal function in F344 rats exposed to several complex EMF exposure metrics. Amplitude and/or time- shift effects will be identified through comparisons of serum melatonin, pineal melatonin, and pineal activity of N-acetyltransferase in EMF- exposed and control rats. EMF metrics to be evaluated will include pure continuous 60 Hz fields, intermittent 60 Hz fields, time-varying 60 Hz fields, pure continuous 180 Hz fields, 60 Hz fields onto which a 180 Hz harmonic has been superimposed, and 60 Hz fields onto which a damped sinusoidal "slow" transient has been superimposed. This approach will identify complex EMF metrics with biological activity; active EMF metrics may have activity as modifiers of human health.