We report results from a multiple linear regression analysis of long-term total ozone observations (1979 to 2002, by TOMS/SBUV), of temperature reanalyses (1958 to 2002, NCEP), and of two chemistry-climate model simulations (1960 to 1999, by ECHAM4.L39(DLR)/CHEM (=E39/C), and MAECHAM4-CHEM). The model runs are transient experiments, where observed sea surface temperatures, increasing source gas concentrations (CO<sub>2</sub>, <i>CFC</i>s, CH<sub>4</sub>, N<sub>2</sub>O, NO<sub>x</sub>), 11-year solar cycle, volcanic aerosols and the quasi-biennial oscillation (QBO) are all accounted for. MAECHAM4-CHEM covers the atmosphere from the surface up to 0.01 hPa (≈80 km). For a proper representation of middle atmosphere (MA) dynamics, it includes a parametrization for momentum deposition by dissipating gravity wave spectra. E39/C, on the other hand, has its top layer centered at 10 hPa (≈30 km). It is targeted on processes near the tropopause, and has more levels in this region. Both models reproduce the observed amplitudes and much of the observed low-latitude patterns of the various modes of interannual variability, MAECHAM4-CHEM somewhat better than E39/C. Total ozone and lower stratospheric temperature show similar patterns. Main contributions to the interannual variations of total ozone and lower stratospheric temperature at 50 hPa come from a linear trend (up to −30 Dobson Units (DU) per decade, or −1.5 K/decade), the QBO (up to 25 DU, or 2.5 K peak to peak), the intensity of the polar vortices (up to 50 DU, or 5 K peak to peak), and from tropospheric weather (up to 30 DU, or 3 K peak to peak). Smaller variations are related to the 11-year solar cycle (generally less than 25 DU, or 2.5 K), and to ENSO (up to 15 DU, or 1.5 K). Volcanic eruptions have resulted in sporadic changes (up to −40 DU, or +3 K). Most stratospheric variations are connected to the troposphere, both in observations and simulations. At low latitudes, patterns are zonally symmetric. At higher latitudes, however, strong, zonally non-symmetric signals are found close to the Aleutian Islands or south of Australia. Such asymmetric features appear in the model runs as well, but often at different longitudes than in the observations. The results point to a key role of the zonally asymmetric Aleutian (or Australian) stratospheric anti-cyclones for interannual variations at high- latitudes, and for coupling between polar vortex strength, QBO, 11-year solar cycle and ENSO.